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Effects of corticosterone on mild auditory fear conditioning and extinction; role of sex and training paradigm.

ABSTRACT: Multiple lines of evidence suggest that glucocorticoid hormones enhance memory consolidation of fearful events. However, most of these studies involve male individuals. Since anxiety, fear, and fear-associated disorders present differently in male and female subjects we investigated in mice whether male and female mice perform differently in a mild, auditory fear conditioning task and tested the modulatory role of glucocorticoid hormones. Using an auditory fear conditioning paradigm with different footshock intensities (0.1, 0.2, and 0.4 mA) and frequencies (1× or 3×), we find that intraperitoneal injections with corticosterone (2 mg/kg) immediately after training, altered freezing behavior when repeated footshocks were applied, and that the direction of the effects were opposite in male and female mice. Effects were independent of footshock intensity. In male mice, corticosterone consistently increased freezing behavior in response to the tone, whereas in female mice, corticosterone reduced freezing behavior 24 h after training. These effects were not related to the phase of the oestrous cycle. In addition, corticosterone enhanced extinction learning for all tones, in both male and female mice. These results emphasize that glucocorticoid hormones influence memory consolidation and retrieval, and underscore sex-specific effects of glucocorticoid hormones in modulating conditioned fear responses.

SUBMITTER: Lesuis SL

PROVIDER: S-EPMC6149954 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for anxiety disorders, affective disorders, and trauma-and stressor-related disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience. Traumatic experiences can lead to long-lasting fear memories and fear potentiation of the acoustic startle reflex. The acoustic startle reflex is an ethologically relevant reflex and can be potentiated in both humans and rats through Pavlovian conditioning. Mycobacterium vaccae is a soil-derived bacterium with immunoregulatory and anti-inflammatory properties that has been demonstrated to enhance fear extinction in the fear-potentiated startle paradigm when given prior to fear conditioning. To determine if immunization with M. vaccae after fear conditioning also has protective effects, adult male Sprague Dawley rats underwent fear conditioning on days -37 and -36 followed by immunizations (3x), once per week beginning 24 h following fear conditioning, with a heat-killed preparation of M. vaccae NCTC 11659 (0.1 mg, s.c., in 100 µl borate-buffered saline) or vehicle, and, then, 3 weeks following the final immunization, were tested in the fear-potentiated startle paradigm (n = 12 per group). Rats underwent fear extinction training on days 1 through 6 followed by spontaneous recovery 14 days later (day 20). Rats were euthanized on day 21 and brain tissue was sectioned for analysis of Tph2, Htr1a, Slc6a4, Slc22a3, and Crhr2 mRNA expression throughout the brainstem dorsal and median raphe nuclei. Immunization with M. vaccae did not affect fear expression on day 1. However, M. vaccae-immunized rats showed enhanced enhanced within-session fear extinction on day 1 and enhanced between-session fear extinction beginning on day 2, relative to vehicle-immunized controls. Immunization with M. vaccae and fear-potentiated startle had minimal effects on serotonergic gene expression when assessed 42 days after the final immunization. Together with previous studies, these data are consistent with the hypothesis that immunoregulatory strategies, such as immunization with M. vaccae, have potential for both prevention and treatment of trauma- and stressor-related psychiatric disorders.

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Effects of corticosterone on mild auditory fear conditioning and extinction; role of sex and training paradigm.

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